The objectives of this project are to design and synthesize the following: (a) Congeners of lead compounds having confirmed activity, to enhance activity or potency; (b) Prodrugs with structural modifications that may provide altered pharmacokinetics, altered drug transport, improved bio-availability through increased water solubility, or increased chemical stability; (c) Other altered structures that possess elements of both congener and prodrug. Modifications of a lead may also include partial structures; and (d) Compounds related to natural products, e.g., alkaloids, heterocycles, nucleosides, peptides, etc. Active leads may also include metal complexes.